2003 Fiscal Year Final Research Report Summary
Development of catalytic asymmetric reactions based on a molecular assembly
| Project/Area Number |
14572001
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TAKEMOTO Yoshiji Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (20227060)
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| Co-Investigator(Kenkyū-buntansha) |
YANADA Reiko Kyoto University, Graduate School of Pharmaceutical Science, Research assistant, 薬学研究科, 助手 (80239821)
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| Project Period (FY) |
2002 – 2003
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| Keywords | quaternary ammonium salt / thiourea / micelle / hydrogen bonding / molecular assembly / iridium / allylic alkylation / Michael addition |
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| Research Abstract |
1.With an aim of proper alignment of the prepared ammonium catalysts in a micelle, we designed and synthesized four ammonium catalysts, which possess alkyl and poly-ether side-chains into the cinchonidine. Although we have developed a convenient method for the introduction of alkyl and poly-ether groups into the cinchonidine-derived quatemary ammonium salts, the asymmetric alkylation of imino glycinate using these catalysts only gave rise to the corresponding products with lower enantioselectivity than that of the original catalyst.
2.We have developed the first enantioselective Ir-catalyzed allylic substitutions of diphenylimino glycinate by using chiral bidentate ligand (up to 98% ee), and also succeeded in the diastereoselective asymmetric synthesis of both diastereomers by simply switching the base employed such as KOH (method A) and LiHMDS (method B).
3.Since we succeeded in the enantioselective synthesis of the branch products, we next investigated the asymmetric synthesis of quaternary amino acids using the Ir-catalyzed allylic alkylation of various alaninates. The adoption of method B to phosphate and alaninate gave chiral quaternary amino acids with acceptable yield and stereoselectivity.
4.We found that thiourea dramatically enhanced the nucleophilic addition of TMSCN and ketene silyl acetals to nitrones and aldehydes. Furthermore, thiourea bearing a tertiary amino group worked well as a bifunctional organocatalyst, and promoted the Michael reaction of malonates to various nitroolefins with high enantioselectivities. The reaction was also successful without solvent.
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